The role of calcium, cyclic GMP and cyclic AMP in the regulation of hydrolase secretion from the rat exocrine pancreas will be explored on tissue fragments, isolated acinar cells and purified plasma membranes. Specific binding and peptide cooperativity of gastrointestinal hormones (such as pancreozymin, secretin, bombesin and somatostatin) will be examined, together with the activity of a guanyl necleotide regulatory site and of membrane-bound adenylate cyclase. Guanylate cyclase, cyclic nucleotide phosphodiesterases (and their calcium-dependent activator), the RC yields reversibly R plus C equilibrium of cyclic AMP and cyclic GMP dependent-protein kinases, and the "phospholipid effect" will also be explored, after treatment with fastrointestinal hormones, muscarinic neurotransmitters (carbamylcholine and pilocarpine), and ionophore A-23187. In addition, calcium accumulation, and the activity of protein kinase(s) and phosphoprotein phosphatase in isolated pancreatic plasma membranes will be documented. Accessorily, the mode of action of pancreatic hydrolases will be investigated, such as the interaction of pancreatic lipase with triglycerides, in the presence of colipase and bile salts.